Brief Summary
This study consists of two parts: phase 2 (Part A) and phase 3 (Part B). It is a multicenter study designed to evaluate the safety, effectiveness, and pharmacokinetics (PK) of CSL889 (human hemopexin) when given intravenously (IV) to adults and adolescents with sickle cell disease (SCD) experiencing vaso-occlusive crises (VOC). The main objectives of the study are to assess how CSL889 affects the time it takes for VOC to resolve in participants with SCD, and to evaluate the safety and tolerability of CSL889 in study participants.
Brief Title
Safety, Efficacy, and Pharmacokinetics of CSL889 in Adults and Adolescents With Sickle Cell Disease During Vaso-Occlusive Crisis
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Sickle Cell Disease Vaso-occlusive Crisis
Eligibility Criteria
Inclusion Criteria:
•At the time of informed consent: \>= 18 years of age (adults); or \>= 12 to less than (\<) 18 years of age (adolescents, where approved and when enrollment for adolescents has been opened by the sponsor, with the endorsement of the Independent Data Monitoring Committee \[IDMC\]).
* Diagnosed with SCD (any genotype).
* Presented at the study site with a new acute VOC necessitating treatment with parenteral opioids.
Exclusion Criteria:
* VOC pain onset greater than or equal to (\>=) 72 hours before administration of first parenteral opioid (Part A; may be adjusted for Part B based on prespecified analysis).
* Must not have a history of greater than (\>) 5 VOCs requiring hospital admission in the past 6 months; or signs and / or symptoms of ACS; or new neurological symptoms suggestive of acute stroke or transient ischemic attack; or any stage (acute kidney injury) AKI; or been discharged from inpatient hospital admission for VOC or other vaso-occlusive event within 14 days before the current presentation.
* Serum hemoglobin \< 6 g/dL, serum ferritin \>= 2000 ng/mL, receiving an approved medication for SCD that has not been on a stable, well-tolerated regimen, currently taking methadone or buprenorphine.
•At the time of informed consent: \>= 18 years of age (adults); or \>= 12 to less than (\<) 18 years of age (adolescents, where approved and when enrollment for adolescents has been opened by the sponsor, with the endorsement of the Independent Data Monitoring Committee \[IDMC\]).
* Diagnosed with SCD (any genotype).
* Presented at the study site with a new acute VOC necessitating treatment with parenteral opioids.
Exclusion Criteria:
* VOC pain onset greater than or equal to (\>=) 72 hours before administration of first parenteral opioid (Part A; may be adjusted for Part B based on prespecified analysis).
* Must not have a history of greater than (\>) 5 VOCs requiring hospital admission in the past 6 months; or signs and / or symptoms of ACS; or new neurological symptoms suggestive of acute stroke or transient ischemic attack; or any stage (acute kidney injury) AKI; or been discharged from inpatient hospital admission for VOC or other vaso-occlusive event within 14 days before the current presentation.
* Serum hemoglobin \< 6 g/dL, serum ferritin \>= 2000 ng/mL, receiving an approved medication for SCD that has not been on a stable, well-tolerated regimen, currently taking methadone or buprenorphine.
Inclusion Criteria
Inclusion Criteria:
•At the time of informed consent: \>= 18 years of age (adults); or \>= 12 to less than (\<) 18 years of age (adolescents, where approved and when enrollment for adolescents has been opened by the sponsor, with the endorsement of the Independent Data Monitoring Committee \[IDMC\]).
* Diagnosed with SCD (any genotype).
* Presented at the study site with a new acute VOC necessitating treatment with parenteral opioids.
•At the time of informed consent: \>= 18 years of age (adults); or \>= 12 to less than (\<) 18 years of age (adolescents, where approved and when enrollment for adolescents has been opened by the sponsor, with the endorsement of the Independent Data Monitoring Committee \[IDMC\]).
* Diagnosed with SCD (any genotype).
* Presented at the study site with a new acute VOC necessitating treatment with parenteral opioids.
Gender
All
Gender Based
false
Keywords
Sickle cell disease
Acute kidney injury
Pharmacokinetics
Acute chest syndrome
Vaso-occlusive crisis
Hemopexin
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Minimum Age
12 Years
NCT Id
NCT06699849
Org Class
Industry
Org Full Name
CSL Behring
Org Study Id
CSL889_2001
Overall Status
Active, not recruiting
Phases
Phase 2
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase 2/Phase 3, Multicenter, Randomized, Multiple-Dose, Double-Blind, Placebo-Controlled Adaptive Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of CSL889 in Adults and Adolescents With Sickle Cell Disease During Vaso-Occlusive Crisis
Primary Outcomes
Outcome Measure
Time to resolution of VOC (time to discontinuation of parenteral opioids)
Outcome Time Frame
Up to Day 28 (End of study [EOS] Visit)
Outcome Measure
Number of participants with treatment-emergent adverse events (TEAEs)
Outcome Time Frame
Up to Day 28 after CSL889 infusion (EOS Visit)
Outcome Measure
Percentage of participants with TEAEs
Outcome Time Frame
Up to Day 28 after CSL889 infusion (EOS Visit)
Outcome Measure
Number of participants with detectable treatment emergent (TE) anti-CSL889 antibodies
Outcome Time Frame
Up to Day 28 after CSL889 infusion (EOS Visit)
Outcome Measure
Percentage of participants with detectable TE anti-CSL889 antibodies
Outcome Time Frame
Up to Day 28 after CSL889 infusion (EOS Visit)
Secondary Ids
Secondary Id
2024-513440-29-00
Secondary Outcomes
Outcome Description
Hospital admission rate in participants with SCD presenting with VOC who received greater than or equal to (\>=) 1 dose of CSL889 in the acute care setting.
Outcome Time Frame
Up to Day 28 after CSL889 infusion (EOS Visit)
Outcome Measure
Hospital admission rate
Outcome Time Frame
Up to Day 28 (EOS Visit)
Outcome Measure
Length of hospital stay (If hospitalized)
Outcome Time Frame
From the start of investigational product (IP) administration up to Day 8
Outcome Measure
Percentage of participants experiencing acute chest syndrome (ACS), acute kidney injury (AKI), or stroke
Outcome Time Frame
Up to Day 28 (EOS Visit)
Outcome Measure
Length of acute care stay
Outcome Time Frame
Up to Day 28 (EOS Visit)
Outcome Measure
Total Length of acute care and hospital stay
Outcome Time Frame
During the 30 days after discharge or at Day 90, whichever comes first
Outcome Measure
Re-presentation rate to an acute care facility for VOC or ACS after discharge
Outcome Time Frame
During the 30 days after discharge or at Day 90, whichever comes first
Outcome Measure
Hospital admission rate for VOC or ACS after discharge
Outcome Description
Opioid consumption will be measured in morphine milligram equivalent units.
Outcome Time Frame
From the time of enrollment to discharge (up to Day 28 [EOS Visit])
Outcome Measure
Opioid consumption
Outcome Description
The Numeric Rating Scale (NRS) for pain is a validated self-reported 11-point pain severity scale (where 0 means no pain and 10 means the most or worst possible pain) that can be used in adults, adolescents, and children \>= 8 years of age with SCD.
Outcome Time Frame
Within 4 hours after the start of CSL889 infusion
Outcome Measure
Percentage of participants with >=30% pain reduction by NRS score
Outcome Time Frame
Before dosing, and up to 12 hours after Doses 1 and 3
Outcome Measure
Maximum observed concentration (Cmax) after Doses 1 and 3 of CSL889
Outcome Time Frame
Before dosing, and up to 12 hours after Doses 1 and 3
Outcome Measure
Area under the concentration (AUCtau) after Doses 1 and 3 of CSL889
Outcome Time Frame
Before dosing, and up to 12 hours after Doses 1 and 3
Outcome Measure
Time of maximum concentration (Tmax) after Doses 1 and 3 of CSL889
Outcome Time Frame
Up to Day 5
Outcome Measure
Trough concentration (Ctrough) after each dose of CSL889
Outcome Time Frame
Before dosing and at up to 12 hours after Doses 1 and 3
Outcome Measure
Accumulation ratio (AR) for AUCtau of CSL889 (the ratio between the AUCtau of Doses 3 and 1)
Outcome Time Frame
Before dosing and at up to 12 hours after Doses 1 and 3
Outcome Measure
AR for Cmax of CSL889 (the ratio between the Cmax of Doses 3 and 1)
Outcome Time Frame
Before dosing and after Dose 1 and the last dose
Outcome Measure
AR for Ctrough of CSL889 (the ratio between the Ctrough of the last dose and Dose 1)
Outcome Description
Sparse PK blood sampling will be performed in Part A participants who are not in the Adult or Adolescent PK Subsets.
Outcome Time Frame
Up to Day 5
Outcome Measure
Ctrough after each dose in sparse PK subset of CSL889
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
12
Investigators
Investigator Type
Principal Investigator
Investigator Name
Ellen Friedman
Investigator Email
elfriedm@montefiore.org
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
Categories Mesh Debug
Blood Disorders --- ANEMIA, SICKLE CELL
Sickle Cell Disorders --- ANEMIA, SICKLE CELL
Blood Disorders --- ANEMIA, HEMOLYTIC, CONGENITAL
Blood Disorders --- ANEMIA, HEMOLYTIC
Blood Disorders --- ANEMIA
Blood & Bone Marrow Cancers --- ANEMIA
Blood Disorders --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- HEMATOLOGIC DISEASES
Kidney & Urinary Tract --- KIDNEY DISEASES
Kidney & Urinary Tract --- UROLOGIC DISEASES
Lung & Chest Cancers --- LUNG DISEASES
COVID-19 --- LUNG DISEASES
Lung --- LUNG DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
Lung & Chest Cancers --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
MeSH Terms
ANEMIA, SICKLE CELL
ACUTE KIDNEY INJURY
ACUTE CHEST SYNDROME
VASO-OCCLUSIVE CRISES
ANEMIA, HEMOLYTIC, CONGENITAL
ANEMIA, HEMOLYTIC
ANEMIA
HEMATOLOGIC DISEASES
HEMIC AND LYMPHATIC DISEASES
HEMOGLOBINOPATHIES
GENETIC DISEASES, INBORN
CONGENITAL, HEREDITARY, AND NEONATAL DISEASES AND ABNORMALITIES
RENAL INSUFFICIENCY
KIDNEY DISEASES
UROLOGIC DISEASES
FEMALE UROGENITAL DISEASES
FEMALE UROGENITAL DISEASES AND PREGNANCY COMPLICATIONS
UROGENITAL DISEASES
MALE UROGENITAL DISEASES
LUNG DISEASES
RESPIRATORY TRACT DISEASES
RESPIRATION DISORDERS
HEMOPEXIN
COUNTERFEIT DRUGS
GLYCOPROTEINS
GLYCOCONJUGATES
CARBOHYDRATES
ACUTE-PHASE PROTEINS
BLOOD PROTEINS
PROTEINS
AMINO ACIDS, PEPTIDES, AND PROTEINS
BETA-GLOBULINS
SERUM GLOBULINS
GLOBULINS
SUBSTANDARD DRUGS
PHARMACEUTICAL PREPARATIONS